CD6 is primarily expressed on T cells. Kamoun et al., J Immunol 127: 987-991 (1981). Results from previous in vitro studies using different CD6-specific monoclonal antibodies (mAbs) are contradictory, suggesting that CD6 can either stimulate or suppress T-cell activation. Bott et al., Int Immunol 5: 783-792 (1993); Singer et al., Immunology 88: 537-543 (1996). CD6 has also long been proposed as a potential target for therapy of autoimmune diseases, and despite the lack of clear understanding of CD6's function, recently a humanized mAb against CD6 has been approved for treating psoriasis in India. Jayaraman, K., Nature Biotechnology 31: 1062-1063 (2013). However, historically, in the United States, the first wave of programs aimed at using CD6-targeted reagents in treating human diseases was dropped or slowed, due in part to the lack of in vivo data to confirm the in vitro and ex vivo studies and to the absence of CD6 gene engineered animals to test CD6-targeted reagents in vivo. Pinto, M. & Carmo, A. M., BioDrugs: clinical immunotherapeutics, biopharmaceuticals and gene therapy 27: 191-202 (2013). So far, there is only one report on in vivo studies of CD6 using genetically engineered animals (Orta-Mascaró, M. et al. J Exp Med 213(8): 1387-1397 (2016)), and the potential role of CD6 in multiple sclerosis (MS) remains elusive. Recent genomic wide association studies from several groups identified CD6 as a risk gene for MS (De Jager et al., Nat Genet 41: 776-782 (2009); Heap et al., Hum Mol Genet 19: 122-134 (2010)), arguing a significant role of CD6 in the pathogenesis of MS.